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Multiple System Atrophy Without Dysautonomia : An Autopsy-Confirmed Study

Wilkens, Ida ; Bebermeier, Sarah ; Heine, Johanne ; Ruf, Viktoria Constanze ; Compta, Yaroslau ; Molina Porcel, Laura ; Troakes, Claire ; Vamanu, Albert ; Downes, Sophia and Irwin, David John , et al. (2025) In Neurology 105(11).
Abstract

BACKGROUND AND OBJECTIVES: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by 3 core symptom complexes: parkinsonism, cerebellar syndrome, and dysautonomia. Recent Movement Disorder Society (MDS) criteria allow for the clinical diagnosis of MSA based solely on motor symptoms, without requiring dysautonomia. This study aimed to evaluate the frequency and disease trajectory of MSA patients without dysautonomia compared with those with autonomic involvement. METHODS: A multicenter cohort of autopsy-confirmed patients with MSA was analyzed for demographic characteristics, symptom onset, and progression of parkinsonism, cerebellar syndrome, and dysautonomia. Clinical data were collected through standardized chart... (More)

BACKGROUND AND OBJECTIVES: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by 3 core symptom complexes: parkinsonism, cerebellar syndrome, and dysautonomia. Recent Movement Disorder Society (MDS) criteria allow for the clinical diagnosis of MSA based solely on motor symptoms, without requiring dysautonomia. This study aimed to evaluate the frequency and disease trajectory of MSA patients without dysautonomia compared with those with autonomic involvement. METHODS: A multicenter cohort of autopsy-confirmed patients with MSA was analyzed for demographic characteristics, symptom onset, and progression of parkinsonism, cerebellar syndrome, and dysautonomia. Clinical data were collected through standardized chart reviews across participating centers and categorized using the MDS-MSA criteria. Patients were grouped according to their initial symptom complex and tracked for the evolution of additional symptoms. Analyses included time to development of further symptom complexes, age at symptom onset, disease duration, and phenotype at the last recorded visit. Patients with motor symptoms only were matched to patients with similar demographics but with dysautonomia. Statistical methods included ANOVA, t tests, Welch t tests, and χ2 tests, with significance set at p < 0.05. RESULTS: Among 140 patients (mean age at onset 62.3 ± 8.9 years; 44% female), 81 (58%) initially presented without dysautonomia (57 with parkinsonism only, 17 with cerebellar syndrome only, 7 with both). At final follow-up, 12 patients (9%) had not developed dysautonomia. These patients showed significantly longer disease duration (mean 8.1 ± 2.1 years) than matched patients with dysautonomia (mean 6.3 ± 2.6 years; p = 0.035). Overall, 51% of patients developed all 3 symptom complexes. Patients with cerebellar onset progressed more rapidly to multisystem involvement than those with parkinsonian onset (mean interval to second symptom: 2.0 vs 3.4 years; p < 0.05). DISCUSSION: The MDS-MSA criteria expand the diagnostic scope by identifying a motor-only subgroup with a distinct and potentially slower disease course. These findings underscore the importance of including motor-only patients in natural history and interventional studies. Limitations include retrospective data collection and potential variability in symptom documentation.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
105
issue
11
article number
e214316
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:41232058
  • scopus:105021797041
ISSN
1526-632X
DOI
10.1212/WNL.0000000000214316
language
English
LU publication?
yes
id
f2ffffec-3bf6-4963-9b6c-e03d73a0f503
date added to LUP
2026-01-13 14:43:30
date last changed
2026-01-13 14:44:42
@article{f2ffffec-3bf6-4963-9b6c-e03d73a0f503,
  abstract     = {{<p>BACKGROUND AND OBJECTIVES: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by 3 core symptom complexes: parkinsonism, cerebellar syndrome, and dysautonomia. Recent Movement Disorder Society (MDS) criteria allow for the clinical diagnosis of MSA based solely on motor symptoms, without requiring dysautonomia. This study aimed to evaluate the frequency and disease trajectory of MSA patients without dysautonomia compared with those with autonomic involvement. METHODS: A multicenter cohort of autopsy-confirmed patients with MSA was analyzed for demographic characteristics, symptom onset, and progression of parkinsonism, cerebellar syndrome, and dysautonomia. Clinical data were collected through standardized chart reviews across participating centers and categorized using the MDS-MSA criteria. Patients were grouped according to their initial symptom complex and tracked for the evolution of additional symptoms. Analyses included time to development of further symptom complexes, age at symptom onset, disease duration, and phenotype at the last recorded visit. Patients with motor symptoms only were matched to patients with similar demographics but with dysautonomia. Statistical methods included ANOVA, t tests, Welch t tests, and χ2 tests, with significance set at p &lt; 0.05. RESULTS: Among 140 patients (mean age at onset 62.3 ± 8.9 years; 44% female), 81 (58%) initially presented without dysautonomia (57 with parkinsonism only, 17 with cerebellar syndrome only, 7 with both). At final follow-up, 12 patients (9%) had not developed dysautonomia. These patients showed significantly longer disease duration (mean 8.1 ± 2.1 years) than matched patients with dysautonomia (mean 6.3 ± 2.6 years; p = 0.035). Overall, 51% of patients developed all 3 symptom complexes. Patients with cerebellar onset progressed more rapidly to multisystem involvement than those with parkinsonian onset (mean interval to second symptom: 2.0 vs 3.4 years; p &lt; 0.05). DISCUSSION: The MDS-MSA criteria expand the diagnostic scope by identifying a motor-only subgroup with a distinct and potentially slower disease course. These findings underscore the importance of including motor-only patients in natural history and interventional studies. Limitations include retrospective data collection and potential variability in symptom documentation.</p>}},
  author       = {{Wilkens, Ida and Bebermeier, Sarah and Heine, Johanne and Ruf, Viktoria Constanze and Compta, Yaroslau and Molina Porcel, Laura and Troakes, Claire and Vamanu, Albert and Downes, Sophia and Irwin, David John and Cohen, Jesse and Lee, Edward B. and Nilsson, Christer F. and Englund, Elisabet M. and Nemati, Mojtaba and Katzdobler, Sabrina and Levin, Johannes and Bernhardt, Alexander Maximilian and Pantelyat, Alexander and Seemiller, Joseph and Berger, Stephen and Van Swieten, John C. and Dopper, Elise G.P. and Rozemuller, Annemieke J.M. and Kovacs, Gabor G. and Bendahan, Nathaniel and Lang, Anthony E. and Herms, Jochen and Höglinger, Günter U. and Hopfner, Franziska}},
  issn         = {{1526-632X}},
  language     = {{eng}},
  number       = {{11}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Neurology}},
  title        = {{Multiple System Atrophy Without Dysautonomia : An Autopsy-Confirmed Study}},
  url          = {{http://dx.doi.org/10.1212/WNL.0000000000214316}},
  doi          = {{10.1212/WNL.0000000000214316}},
  volume       = {{105}},
  year         = {{2025}},
}